The specific aims are to localize and further characterize HCO3- absorption and HCO3- secretion by specific cells of the intestinal mucosa using ion-selective microelectrodes, pH stat and other techniques and to test specific models postulated for HCO3- transport, and the enhanced secretion following exposure to cyclic AMP. The relationship between intracellular pH measured with liquid ion-exchange microelectrodes and HCO3- absorption measured by pH stat will be determined in in vitro segments of Amphiuma jejunum. The postulate that H+ secretion is linked to K+ uptake will be tested in detail and the role of intracellular Na+ in influencing the rate of HCO3- absorption will be assessed with Na+ sensitive microelectrodes. The possibility that acetazolamide, DIDS and cyclic AMP alter HCO3- absorption by changes in intracellular pH will be tested. The role of basolateral Na/H exchange in duodenal HCO3- secretion and the electrogenic secretion induced by theophylline will be investigated with Na+- specific microelectrodes. The effect of cholera toxin on HCO3- secretion as well as HCO3- absorption will be studied in detail. The ion transport underlying the electrically silent secretion of HCO3- induced by secretin and glucagon will be characterized. The influence of different hormones and neurotransmitters on HCO3- transport will be determined. The contribution of villus and intervillus (crypt) regions of the mucosa to HCO3- absorption and secretion will be measured directly by pH stat. Finally brush border membranes will be isolated and assayed for K+, HCO3- and Cl- stimulated ATPase activity. The results of this study will provide a better understanding of the mechanisms and control of K+, CL- and HCO3 absorption and the secretion of HCO3-. From a clinical perspective the studies are important for understanding the etiology of duodenal ulcers as well as diarrheal diseases including cholera and chloride diarrhea.